Methods

We retrospectively identified 507 consecutive patients with RP from 2007 to 2011 in the Cleveland Clinic’s Center for Pericardial Disease database. RP was defined as recurrence of pericarditis <6 weeks after weaning of anti-inflammatory medications. This definition was based on the European Society of Cardiology guidelines on the diagnosis and management of pericardial diseases, published in 2004.

All patients ≥18 years of age who developed recurrence of pericarditis symptoms after the first attack of pericarditis were included in the study. All patients were treated initially with colchicine and NSAID as the first-line therapy and started on steroids after the first recurrence. Patients who were not started on colchicine and NSAID as first-line therapy or treated with steroids at the initial diagnosis were excluded from the study (n = 106; Figure 1 ). Patients were then stratified as those who did not undergo CMR during the course of treatment (group 1) and those who did (group 2). All patients were treated with standard therapy on the basis of the European Society of Cardiology guidelines and most recently published studies related to RP.

Selection of patients for retrospective analysis.

The decision to order CMR was at the discretion of the treating cardiologist. Patients with RP who were seen in the pericardial disease center clinic were subject to CMR compared with patients seen in general cardiology clinic. CMR studies with LGE were performed using a standard protocol, as previously described in detail and interpreted by level III trained and certified cardiologists. In summary, a comprehensive pericardial CMR protocol should include morphologic evaluation of the cardiac chambers, pericardium, and mediastinum using fast spin-echo T1-weighted sequences with black-blood preparation; assessment of global and regional systolic function of the left and right ventricles, using cine steady-state free precession sequences; depiction of pericardial fluid and/or edema using T2-weighted spin-echo imaging, preferably by using short-tau inversion-recovery sequences; ventricular coupling using real-time free-breathing cine sequences; and tissue characterization using LGE inversion-recovery CMR. All patients with initial CMR had ≥2 sequential studies to follow disease activity and response to treatment. LGE changes with subsequent studies were assessed to confirm inflammation activity and changes of LGE in response to treatment intervention. During acute inflammation, T2-weighted short-tau inversion recovery imaging detects fluid and/or edema of the inflamed pericardial layers, and delayed enhancement imaging further shows brighter signal of inflamed pericardium. Decreased pericardial edema, brightness, and thickness were qualitatively used as parameters for response to medical therapy ( Figure 2 ).

CMR of a patient with RP. (A) Clearly active inflammation ( white arrow ) using T2-weighted short-tau inversion recovery imaging with pericardial effusion. (B) The same patient, with LGE technique showing active inflammation involving most of the pericardium ( white arrow ). (C) CMR of the same patient after 5 months of medical therapy and off steroids, with resolution of inflammation and no LGE (D) .

There were several primary end points of interest: total number of milligrams of steroid used over the course of the disease, number of steroid pulse therapies, number of recurrences, and complications (constrictive pericarditis, pericardial windows, pericardiocentesis, pericardiectomy, and all-cause mortality). Steroid pulse therapy was defined as prednisone ≥50 mg administered orally daily for 10 days then tapered to none over a 4-week period.

Descriptive analyses were performed examining selected variables for each group. Continuous variables are expressed as mean ± SD or median (interquartile range) and were compared using unpaired Student’s t tests or Wilcoxon’s rank tests as appropriate. Categorical variable are expressed as number (percentage) and were compared using Pearson’s chi-square tests or Fisher’s exact tests as appropriate. Linear regression modeling was performed to assess the independent predictors of number of steroid pulses. The model was adjusted for baseline demographics, co-morbidities, history of recurrence, and CMR. A p value <0.05 was set a priori and considered statistically significant. All statistical analyses were performed using SPSS version 19 for Windows (SPSS, Inc., Chicago, Illinois). The study was approved by the institutional review board with waiver of the requirement for informed consent and complied with the Declaration of Helsinki.

Results

The study cohort consisted of 507 patients (mean age 48 ± 14 years, 50.2% men) who met the inclusion criteria with the diagnosis of RP ( Figure 1 ). All patients were treated initially with colchicine and NSAIDs followed by oral steroids and continued for the whole treatment period ( Table 1 ). Almost half of the cohort received CMR-guided therapy. There were no contraindications to CMR in either group (i.e., acute or chronic renal failure, allergy to gadolinium contrast). Furthermore, there were no significant differences in demographics, baseline co-morbidities, cause of disease, and medication use between the groups ( Table 1 ). The 2 groups had similar follow-up periods (mean 17 ± 7.9 vs 16.3 ± 6.2 months, p = 0.97).

After a mean follow-up time of 17 months, patients who had no CMR done (group 2) had a larger number of steroid pulse therapies (2.41 ± 1.06 vs 0.63 ± 0.91, p = 0.0001) and higher overall total milligrams of steroid administered (1,695.4 ± 1,166.09 vs 486 ± 546.4, p = 0.0001) compared with those who received CMR-guided therapy (group 1). Furthermore, patients in group 2 had more recurrence of symptoms (p = 0.001) and pericardiocentesis (p = 0.001) ( Table 2 ). There was no significant difference in the occurrence of pericardial window, constrictive pericarditis, pericardiectomy, or death between the groups. The duration of therapy needed for complete resolution of recurrence (freedom from disease) was 6 ± 2.1 months in group 1 compared with 13 ± 3.2 months in group 2 (p = 0.001).

Table 2

Outcomes of patients with recurrent pericarditis stratified by cardiac magnetic resonance guided therapy

Variable	Managed With Cardiac Magnetic Resonance Imaging		P
	Yes (n = 257)	No (n = 250)
Mean WSR (SD), (mm/hr)	32.0±27.2	32.3±27.9	0.89
Number of prednisone pulses (SD)	0.63±0.91	2.41±1.06	<0.0001
Total prednisone (SD), (mg)	486±546	1695.4±1166	<0.0001
Number of recurrences, (SD)	1.19±1.2	3.6±2.18	<0.0001
Mean glycated hemoglobin, HbA1c, (SD)(%)	7.4±0.6	9.3±1.2	<0.0001
Constrictive pericarditis	19 (7.4%)	17 (6.8%)	0.86
Pericardiocentesis	15 (5.8%)	40 (16%)	<0.0001
Pericardial Window	56 (21.8%)	44 (17.6%)	0.26
Pericardiectomy	12 (4.7)	14 (5.6)	0.69
Death	1 (0.4%)	2 (0.8%)	0.61

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